Computational modeling of capillary electrophoretic behavior of primary amines using dual system of 18-crown-6 and β-cyclodextrin

Using capillary electrophoresis (CE) three chiral primary amine compounds 1-aminoindan (Al), 1-(1-naphthyl)ethylamine (NEA) and 1,2,3,4-tetrahydro-1-naphthylamine (THAN), exhibited only partial or no separation when beta-cyclodextrin (beta CD) was used as chiral selector. The use of 18-crown-6 (18C6) as a second additive with beta CD resulted in an enhanced separation. A molecular modeling study, using molecular mechanics and the semiempirical PM6 calculations, was used to help explaining the mechanism of the enantiodifferentiation and to predict the separation process. Optimization of the structures of the complexes by the PM6 method indicate that the poor separation obtained in the presence of the beta CD chiral selector alone is due to the small binding energy differences (Delta Delta E) of 4.7, 1.1 and 1.2 kcal mol(-1) for Al, NEA and THAN, respectively. In the presence of 18C6 it was suggested that a sandwich compound between 18C6, amine and beta CD is formed. Theoretical calculations show that a significant increase in the binding energy is obtained for the sandwich compounds indicating strong hydrophobic and van der Waals interactions that show enhanced enantiodifferentiation. (C) 2011 Elsevier By. All rights reserved.